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Special Issue "SAR "Out of the Box": From Pharmacological Drug Design to Cellular Activity of Biomolecules from Plants and Bacteria to Animals"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (26 May 2019).

Special Issue Editors

Prof. Dr. Laurence Lins
E-Mail Website
Guest Editor
Laboratory of Molecular Biophysics at Interfaces, Gembloux Agro-Bio Tech, University of Liège, Passage des déportés, B-5030 Gembloux, Belgium
Interests: molecular modelling, protein sequence analysis, protein and peptide–lipid interaction, membrane interaction, structure–activity reationships (SAR), molecular biophysics
Special Issues and Collections in MDPI journals
Dr. Magali Deleu
E-Mail Website
Guest Editor
Laboratory of Molecular Biophysics at Interfaces, Gembloux Agro-Bio Tech, University of Liège, Passage des déportés, B-5030 Gembloux, Belgium
Interests: amphiphilic molecules, biomimetic membranes, membrane interactions, in vitro molecular biophysics, molecular mechanisms, structure–activity relationships, lipid specificity

Special Issue Information

Dear colleagues,

Classically, the structure–activity relationship (SAR) is an approach designed to find relationships between the chemical structure (or structural-related properties), 3D structure, and biological activity of studied compounds, as defined by Crum-Brown and Fraser in 1865. This is because similar compounds should have similar physico-chemical and biological properties. If this notion is almost always associated with pharmacological drug design and the assessment of side effects of existing compounds in the human health field, it can actually be extended to a large number of bioactive molecules exerting a number of cellular activities. For instance, interactions between plant or bacterial secondary metabolites as well as proteins belonging to the same structural family could have differential activities at the level of the cellular membrane. This Special Issue is dedicated to widening the notion of SAR to a more general concept concerning the relationships between structure and activity of bioactive molecules belonging to all living organisms, whether they have pharmacological effects or not.

Prof. Dr. Laurence Lins
Dr. Magali Deleu
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • membrane activity of biomolecules
  • synthesis/hemisynthesis of bioactive molecules
  • chemical characterization of biomolecules related to their activity
  • protein structure–activity relationships
  • secondary metabolite structure–biological activity relationships
  • drug design

Published Papers (5 papers)

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Research

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Article
Insights into the Relationships Between Herbicide Activities, Molecular Structure and Membrane Interaction of Cinnamon and Citronella Essential Oils Components
Int. J. Mol. Sci. 2019, 20(16), 4007; https://doi.org/10.3390/ijms20164007 - 16 Aug 2019
Cited by 15 | Viewed by 1524
Abstract
Since the 50’s, the massive and “environmental naïve” use of synthetic chemistry has revolutionized the farming community facing the dramatic growth of demography. However, nowadays, the controversy grows regarding the long-term harmful effects of these products on human health and the environment. In [...] Read more.
Since the 50’s, the massive and “environmental naïve” use of synthetic chemistry has revolutionized the farming community facing the dramatic growth of demography. However, nowadays, the controversy grows regarding the long-term harmful effects of these products on human health and the environment. In this context, the use of essential oils (EOs) could be an alternative to chemical products and a better understanding of their mode of biological action for new and optimal applications is of importance. Indeed, if the biocidal effects of some EOs or their components have been at least partly elucidated at the molecular level, very little is currently known regarding their mechanism of action as herbicides at the molecular level. Here, we showed that cinnamon and Java citronella essential oils and some of their main components, i.e.,, cinnamaldehyde (CIN), citronellal (CitA), and citronellol (CitO) could act as efficient herbicides when spread on A. thaliana leaves. The individual EO molecules are small amphiphiles, allowing for them to cross the mesh of cell wall and directly interact with the plant plasma membrane (PPM), which is one of the potential cellular targets of EOs. Hence, we investigated and characterized their interaction with biomimetic PPM while using an integrative biophysical approach. If CitO and CitA, maintaining a similar chemical structure, are able to interact with the model membranes without permeabilizing effect, CIN belonging to the phenylpropanoid family, is not. We suggested that different mechanisms of action for the two types of molecules can occur: while the monoterpenes could disturb the lipid organization and/or domain formation, the phenylpropanoid CIN could interact with membrane receptors. Full article
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Article
Mucin Thin Layers: A Model for Mucus-Covered Tissues
Int. J. Mol. Sci. 2019, 20(15), 3712; https://doi.org/10.3390/ijms20153712 - 29 Jul 2019
Cited by 1 | Viewed by 1281
Abstract
The fate of macromolecules of biological or pharmacological interest that enter the mucus barrier is a current field of investigation. Studies of the interaction between the main constituent of mucus, mucins, and molecules involved in topical transmucoidal drug or gene delivery is a [...] Read more.
The fate of macromolecules of biological or pharmacological interest that enter the mucus barrier is a current field of investigation. Studies of the interaction between the main constituent of mucus, mucins, and molecules involved in topical transmucoidal drug or gene delivery is a prerequisite for nanomedicine design. We studied the interaction of mucin with the bio-inspired arginine-derived amphoteric polymer d,l-ARGO7 by applying complementary techniques. Small angle X-ray scattering in bulk unveiled the formation of hundreds of nanometer-sized clusters, phase separated from the mucin mesh. Quartz microbalance with dissipation and neutron reflectometry measurements on thin mucin layers deposited on silica supports highlighted the occurrence of polymer interaction with mucin on the molecular scale. Rinsing procedures on both experimental set ups showed that interaction induces alteration of the deposited hydrogel. We succeeded in building up a new significant model for epithelial tissues covered by mucus, obtaining the deposition of a mucin layer 20 Å thick on the top of a glycolipid enriched phospholipid single membrane, suitable to be investigated by neutron reflectometry. The model is applicable to unveil the cross structural details of mucus-covered epithelia in interaction with macromolecules within the Å discreteness. Full article
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Article
Design and Synthesis of a New Soluble Natural β-Carboline Derivative for Preclinical Study by Intravenous Injection
Int. J. Mol. Sci. 2019, 20(6), 1491; https://doi.org/10.3390/ijms20061491 - 25 Mar 2019
Cited by 6 | Viewed by 1207
Abstract
Harmine is a natural β-carboline compound showing several biological activities, including antiproliferative properties, but this soluble natural molecule lacks selectivity. Harmine derivatives were reported to overcome this problem, but they are usually poorly soluble. Here, we designed and synthesized a new 2, 7, [...] Read more.
Harmine is a natural β-carboline compound showing several biological activities, including antiproliferative properties, but this soluble natural molecule lacks selectivity. Harmine derivatives were reported to overcome this problem, but they are usually poorly soluble. Here, we designed and synthesized a new 2, 7, 9-trisubstituted molecule (1-methyl-7-(3-methylbutoxy)-9-propyl-2-[(pyridin-2-yl)methyl]-9H-pyrido[3,4-b]indol-2-ium bromide) with a solubility of 1.87 ± 0.07 mg/mL in a simulated injection vehicle. This compound is stable for at least 72 h in acidic and physiological conditions (pH 1.1 and 7.4) as well as in a simulated injection vehicle (physiological liquid + 0.1% Tween80®). Solubility in those media is 1.06 ± 0.08 mg/mL and 1.62 ± 0.13 mg/mL at pH 7.4 and 1. The synthesized molecule displays a significant activity on five different cancer cell lines (IC50 range from 0.2 to 2 µM on A549, MDA-MB-231, PANC-1, T98G and Hs683 cell lines). This compound is also more active on cancer cells (MDA-MB-231) than on normal cells (MCF-10a) at IC50 concentrations. Due to its high activity at low concentration, such solubility values should be sufficient for further in vivo antitumoral activity evaluation via intravenous injection. Full article
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Article
Exploring the Dual Interaction of Natural Rhamnolipids with Plant and Fungal Biomimetic Plasma Membranes through Biophysical Studies
Int. J. Mol. Sci. 2019, 20(5), 1009; https://doi.org/10.3390/ijms20051009 - 26 Feb 2019
Cited by 13 | Viewed by 1633
Abstract
Rhamnolipids (RLs) are potential biocontrol agents for crop culture protection. Their mode of action has been proposed as dual, combining plant protection activation and antifungal activities. The present work focuses on the interaction of natural RLs with plant and fungi membrane models at [...] Read more.
Rhamnolipids (RLs) are potential biocontrol agents for crop culture protection. Their mode of action has been proposed as dual, combining plant protection activation and antifungal activities. The present work focuses on the interaction of natural RLs with plant and fungi membrane models at the molecular scale. Representative models were constructed and the interaction with RLs was studied by Fourier transform infrared (FTIR) and deuterium nuclear magnetic resonance (2H NMR) spectroscopic measurements. Molecular dynamic (MD) simulations were performed to investigate RL insertion in lipid bilayers. Our results showed that the RLs fit into the membrane models and were located near the lipid phosphate group of the phospholipid bilayers, nearby phospholipid glycerol backbones. The results obtained with plant plasma membrane models suggest that the insertion of RLs inside the lipid bilayer did not significantly affect lipid dynamics. Oppositely, a clear fluidity increase of fungi membrane models was observed. This effect was related to the presence and the specific structure of ergosterol. The nature of the phytosterols could also influence the RL effect on plant plasma membrane destabilization. Subtle changes in lipid dynamics could then be linked with plant defense induction and the more drastic effects associated with fungal membrane destabilization. Full article
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Review

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Review
Is It Possible to Predict the Odor of a Molecule on the Basis of its Structure?
Int. J. Mol. Sci. 2019, 20(12), 3018; https://doi.org/10.3390/ijms20123018 - 20 Jun 2019
Cited by 10 | Viewed by 3044
Abstract
The olfactory sense is the dominant sensory perception for many animals. When Richard Axel and Linda B. Buck received the Nobel Prize in 2004 for discovering the G protein-coupled receptors’ role in olfactory cells, they highlighted the importance of olfaction to the scientific [...] Read more.
The olfactory sense is the dominant sensory perception for many animals. When Richard Axel and Linda B. Buck received the Nobel Prize in 2004 for discovering the G protein-coupled receptors’ role in olfactory cells, they highlighted the importance of olfaction to the scientific community. Several theories have tried to explain how cells are able to distinguish such a wide variety of odorant molecules in a complex context in which enantiomers can result in completely different perceptions and structurally different molecules. Moreover, sex, age, cultural origin, and individual differences contribute to odor perception variations that complicate the picture. In this article, recent advances in olfaction theory are presented, and future trends in human olfaction such as structure-based odor prediction and artificial sniffing are discussed at the frontiers of chemistry, physiology, neurobiology, and machine learning. Full article
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